Reproductive success of all animals depends on the development and function of the gonads, which are responsible for producing and delivering eggs and sperm. Among humans, ovarian integrity and output are key determinants of health, fertility and fecundity. Understanding how animals regulate ovarian development is therefore critical to advance biomedical research. The cells that will become the ovary are first set aside in embryonic development in both humans and fruit flies. They then proliferate throughout fetal development in humans, and larval development in flies. Germ cells, which will go on to produce eggs and sperm, also proliferate during this time, in close contact with the somatic cells of the ovary. It is thought that germ cell and somatic cell proliferation are coordinated, but the detailsof this coordination are poorly understood. Incorrect proliferation of either cell type can lead to tumors and ovarian cancer, which often cause sterility in humans. It is therefore clear that the coordination of growth in different ovarian cell types is a critical determinant of fertility and reproductive health, but we do not know how this growth is regulated so that the proper number of each cell type is achieved. The specific Aims of this project are (1) to understand the developmental processes that cells undergo during early ovarian development; (2) to understand the role in this process of a signaling pathway called the Hippo pathway, which is strongly implicated in many human cancers; (3) to understand how the Hippo pathway interacts with other genes to direct ovarian development. For the first Aim, we have compared ovarian development in fly species with very different ovariole numbers. This has taught us that there are two critical stages of development that future work should be focused on: first, the earliest stages of embryogenesis when cells are first set aside; and second, the later period when these cells proliferate to create the correct number of cells needed to make ovarioles. For our second Aim, we will investigate how the Hippo pathway functions during normal ovarian development. Mutations in Hippo pathway genes are linked to several types of human cancers, including cancers of the ovary and reproductive system in humans. Finally, for our third Aim, we examine the other potential signaling and growth genes that the Hippo pathway interacts with to direct ovarian development. This has clear relevance to human health, since several reproductive disorders and cancers are associated with defective Hippo signaling. Understanding more about the role of Hippo signaling in normal ovarian development is thus an important priority in our research.